This trial is active, not recruiting.

Condition malaria
Treatments fosmidomycin, azithromycin
Phase phase 2
Sponsor Jomaa Pharma GmbH
Collaborator Mahidol University
Start date November 2008
End date October 2009
Trial size 43 participants
Trial identifier NCT01464125, JP011


The aim of this study is to evaluate the role of azithromycin as a possible combination partner for fosmidomycin to protect it from its susceptibility to recrudescent infections when used as monotherapy for acute Plasmodium falciparum malaria while retaining its excellent safety profile.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Open label single arm concurrent administration of fosmidomycin and azithromycin.
Fosmidomycin sodium capsules 450 mg x 4 twelve-hourly for three days
Azithromycin capsules 250 mg x 3 twelve-hourly for three days

Primary Outcomes

day 28 cure rate of >95%
time frame: 12 months
Safety and Tolerance
time frame: 12 months
Day 7 cure rate of 100%
time frame: 12 months

Secondary Outcomes

Blood samples at 0,1,2,3,4,6,8,12,14,18,24, 26,30,36,38,42,48,50,54,60,62,66,72,78,84,90,96,108,120,144.168.240 hours
time frame: 12 months
PCR corrected cure rates
time frame: 12 months

Eligibility Criteria

Male or female participants from 15 years up to 55 years old.

Inclusion Criteria: - male and female subjects aged 15 to 55 years - body mass index ≥ 18.5kg/M2 - uncomplicated P falciparum malaria with acute manifestations - asexual parasitaemia between 500uL and 100,000uL - ability to tolerate oral therapy - able to give informed signed consent Exclusion Criteria: - signs of severe malaria, according to WHO criteria - body mass index ≤ 18.5 kg/M2 - pregnancy by history or by positive urine test - lactation - mixed plasmodial infection - concomitant disease masking assessment of response, including diabetes, uncontrolled hypertension, heart failure, hepatic dysfunction (alanine-amino transferase > 150 U/L), renal impairment (creatinine > 125 umol/L or 3 mg/dl), haemoglobin < 8g/dl, white cell count > 12000/uL - anti-malarial treatment within previous 28 days - symptomatic AIDS

Additional Information

Official title Evaluation of Fosmidomycin and Azithromycin When Administered Concurrently to Adult Subjects With Acute Uncomplicated Plasmodium Falciparum Malaria
Principal investigator Srivicha Krudsood, Prof
Description The scientific rationale for the use of this combination is to inhibit the ability of the parasite to synthesise isoprenoids, as precursors of many essential compounds including sterols, carotenoids and ubiquinones. This is effected through blockade of the non-mevalonate pathway by fosmidomycin as a potent inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase coupled with targeting of protein biosynthesis by azithromycin through binding to the 50S ribosomal subunit. This mode of action contrasts with the ability of the human host to utilise the mevalonate pathway for isoprenoid synthesis and accounts for the safety profiles of both drugs through the mechanism of selective toxicity. Moreover it affords protection against cross resistance with existing chemotherapeutic agents. The dose of fosmidomycin, equivalent to 30mg/kg twice daily for three days, selected for evaluation in this proof of concept study is derived from the highest dose that was administered in the Phase I safety tolerance studies. While the recommended dose of azithromycin for the treatment of bacterial infections is 250mg daily for three days, higher doses of up to 1500mg daily for three days have been evaluated for the treatment of malaria, in combination with artesunate or quinine.
Trial information was received from ClinicalTrials.gov and was last updated in October 2011.
Information provided to ClinicalTrials.gov by Jomaa Pharma GmbH.